Geris Flashcards
How sensitive and specific is CAM (Confusion Assessment Method)
What does it involve?
94% sensitive, 89% specific
Acute onset, Inattention + either impaired consciousness or disorganised thinking
How to differentiate between delirium and dementia?
Delirium: acute, fluctuating, not orientated, impaired attention
Dementia: insidious onset, progressive, attention normally intact
What does the timed up and go test assess?
Mobility, balance and falls risk
Normal < 10s
Increased risk of falls in community dwelling adults >13.5s
Assesses falls risk
82yo mane presents with difficulty walking due to OA in his right hip. When prescribing a single point stick as a walking aide for him, the most appropriate instruction regarding use of the cane is:
Hold the cane on left hand and advance SPS with right leg - hold SPS in the “good” hand and advance with SPS with the ‘bad” leg
CADASIL - cerebral autosomal dominant arteriopathy with subcortical infarcts and leukenoencephalopathy
lacunar infarct, family history of dementia, dementia at young age, white matter disease, notch 3 gene, chromosome 19
Signs of normal pressure hydrocephalus
Cognitive impairment
Urinary incontinence
Dyspraxic gait
In Lewy Body dementia, what develops first - the dementia or parksinsons?
Dementia occurs first and then parkinsons later
What can help diagnose lewy body dementia?
SPECT scan - sensitivity 90%, specificity 100%
Low dopamine transporter uptake in basal ganglia on SPECT
3 types of frontotemporal lobar degeneration
- Frontotemporal dementia (Pick’s disease)
- Progressive non fluent aphasia (chronic progressive aphasia, CPA)
- Semantic dementia
Name 3 cholinesterase inhibitors use to treated Alzheimers
Donepezil
Rivastigamine
Galantamine
“Dona Riva dances at the nursing home gala:” Donepezil, rivastigmine, and galantamine.
Benefit of cholinesterase inhibitors in Alzheimers
Improve cognitive function and improvement in activities of daily living
Adverse effects of cholinesterase inhibitors
- GIT symptoms: upset stomach, nausea, diarrhoea, anorexia, weight loss occurs in 20-30% of patients
Toxicity dose related, often resolves with time and dose reduction - Bradycardia from cholinergic toxicity
- Headaches
- Sleep disturbances like insomnia, vivid dreams, nightmares(happens with donepezil)
- Can worsen urge incontinence
- rarely rhabdo and NMS
Contraindications of cholinesterase inhibitors
Bradycardia, sick sinus syndrome, heart block, risk of fall/syncope/fractures
Mechanism of action of memantine and SE
NMDA antagonist used for moderate to severe Alzheimers
SE: headaches, dizziness, confusion, hallucinations , seizures
Should not use anticholinergic substances, eg: tricyclic antidepressants
Pathology of AD
- Neuritic plaques (amyloid beta) accumulating extracellularly
- Neurofibrillary tangles (phosphorylated tau) accumulating intracellularly
What infarcts are normally seen in vascular dementia?
Lacunar infarcts
What might be see on the SPECT scan for LBD?
Decreased occipital perfusion/metabolism
Pathology of lewy body dementia
a-synuclein
What might be see on the SPECT scan for frontotemporal dementia
Metabolic disorders in frontal and temporal lobes
What is order of language impairment in AD
naming - comprehension - fluency
Gene involved in familial alzheimer’s disease and what chromsome it is located on
PSEN1 on chromosome 14
What chromosome is amyloid precursor protein located on?
chromosome 21
Which allele has the strongest association with Alzheimer’s Disease
APOE4 alleles have the strongest associated with AD. Located on chromosome 19. one copy of E4 = 2x increased risk, 2 copies of E4 = 8x increased risk
Which dementia are associated with tau?
Corticobasal degeneratin
Alzheimer’s Disease
Progressive supranuclear palsy
T-CAP
Which dementia is associated with a-synuclein
Lewy body dementia
Parkinsons disease
Multisystem atrophy
(PALM)
What dementia is associated with TDP43
Motor neuron disease
Limbic predominant age (LATE)
Frontotemporal dementia - primary progressive aphasia
Pathophysiology of AD
Defining features of AD
- Extraneuronal amyloid-β (Aβ) plaques [gun]
- Neurofibrillary tangles (hyperphosphorylated tau) [bullet] - the main cause of AD
Microglia-mediated inflammation Neuronal loss (inflammatory, oxidative)
How are amyloid B plaques produced in alzheimer’s disease
Produced by proteolysis of transmembrane protein APP (amyloid precursor protein) by β and ɣ secretase enzy
Disease burden of AD is dependent on what?
Severity of cognitive decline correlates more closely with NFT burden than with amount of amyloid deposition
What areas of the brain are affected with neurofibrillary tangle pathology (tau)?
Entorhinal cortex (medial temporal lobe) > hippocampus >neocortex
Quantity of B amyloid does not correspond to progression and severity of disease. T/F?
T
• Quantity does not correspond to progression and severity of disease
• Amyloid plaques commonly found in normal older adults
• Pharmacological clearance of amyloid-B has not resulted in improved cognition or ADLs
•Accumulating amyloid-B induces the spread of tau pathology (amyloid is the gun and tau is the bullet)
•Severity of cognitive decline correlates more closely with NFT burden than with amount of amyloid deposition
What imaging modality should be used to diagnose vascular dementia?
Vascular dementia is the only dementia subtype where MRI is superior to CT, as cortical and subcortical ischaemic lesions are better demonstrated, and some vascular pathologies such as micro-bleeds may be otherwise missed.
Difference between cerebral amyloid angiopathy and hypertensive bleeds.
- Cerebral amyloid angiopathy characterised by haemorrhages in the cortex or subcortical white matter (lobar locations) with sparing of the basal ganglia and brainstem
- In contrast, non-lobar haemorrhages or basal ganglia bleeds can be due to htn.
What are the findings of lewy body dementia on spect?
decreased dopamine transporter uptake in basal ganglia on spect (sensitivity 90%, specificity 100%)
What are features of lewy body dementia?
- Dementia - impairments most in attention/concentration, executive function, visuospatial/constructional impairment instead of memory loss like in AD
- Cognitive fluctuations
Spontaneous and marked variations in cognition function, frequently accompanied by changes in alertness/arousal/consciousness
‘Staring spells’, ‘appears vague or blank’, ‘unresponsive but
awake’, ‘confusion alternating with lucidity - Visual hallucinations - children and animals
- Parkinsonism
- REM sleep behaviour disorder
What chromosome links familial FTD and amyotrophic lateral sclerosis (ALS)?
C9ORF72 (chromosome 9 opening reading frame 72)
Indication of cholinesterase inhibitors
First-line treatment for Alzheimer dementia (particularly mild to moderate stages - MMSE 10-26) and vascular dementia.
Recommended for: Alzheimer disease, vascular dementia, lewy body dementia, parkinson disease dementia.
Not supported for:
Mild cognitive impairment
Frontotemporal dementia
Huntington disease
MS
Indication of memantine
Particularly used in moderate to advanced cases (MMSE <10 or 10-14) of Alzheimer disease or vascular dementia
Aducanumab
Aducanumab is a human, immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid beta.
For Alzheimer’s dementia
Function of limbic cortex
Mood
Sleep + appetite
Attention + alertness
Genetic factors associated with dementia
- Down Syndrome (trisomy 21)
- Amyloid precursor protein (APP): chromosome 21
- Presenilin-1 (PSEN1): chromosome 14 (most common)
- Presenilin 2 (PSEN2): chromosome 1
Potentially modifiable RF for dementia
Early Life: Less education
Midlife: Hearing loss, traumatic brain injury, HTN, Alcohol, Obesity (in order)
Late Life: smoking, depression, social isolation, physical inactivity, air pollution, diabetes (in order)
Variants of frontotemporal dementia and their features
(A) BEHAVIOURAL variant FTD
(B) LANGUAGE
(1) Semantic variant progressive primary progressive aphasia
- Issues with naming recognised objects, people and places
, slowly lose the knowledge of what the words mean
- Left anterior temporal atrophy
- Pathology: TDP 43
(2) Non-fluent/agrammatic variant primary progressive aphasia
- Gradual loss of ability to speak, read and write - can’t express themselves despite knowing the words, difficulty pronouncing words
- Left posterior fronto-insular atrophy
- Pathology: FTLD-T
(3) Logopenic variant primary progressive aphasia
- Left posterior temporal and inferior parietal atrophy
Causes of rapidly progressive dementia
- CJD
- Neurodegenerative: Alzheimer’s, FTD, DLB
- Vascular
- Infectious: HIV, HSV-1, PML, TB, fungal, parasitic
- Toxic: vitamins, alcohol, organ failure, heavy metals
- Immunological / paraneoplastic
- Malignant: CNS lymphoma
- Iatrogenic due to hypotension, drugs, radiation
- Seizures
Mutations in the PSEN1 gene are the most common cause of familial AD. On which chromosome is PSEN1 gene found? A. Chromosome 1 B. Chromosome 8 C. Chromosome 14 D. Chromosome 19 E. Chromosome 21
C. Chromosome 14
The deposition of amyloid B plaques and neurofibillary tangles are 2 of the cellular hallmarks in the pathophysiology of AD. Which of the statements is not true?
A. Amyloid plaques are commonly found in normal older adults
B. The severity of cognitive decline correlates more closely with the amount of amyloid B then with neurofibrillary tangle burden
C. Amyloid plaques are produced by the proteolysis of transmembrane amyloid precursor protein by B and Y secretase enzymes
D. Tau promote stabilisation of intracellular microtubules in neurons
E. The entorhinal cortex is one of the earlies regions affected with neurofibillary tangle pathology
B. The severity of cognitive decline correlates more closely with the amount of amyloid B then with neurofibrillary tangle burden
Which of the following modifiable midlife RF account for the greatest risk of developing dementia in later life? A. TBI B. HTN C. Excess alcohol consumption D. Obesity E. Hearing loss
E - hearing loss
Which of the following would not be considered diagnostic for dementia with LB?
A. Cognitive fluctuations + severe neuroleptic sensitivity
B. Cognitive fluctuations + reduced uptake in BG on DAT scan
C. Parkinsonism + REM sleep behaviour disorder
D. Visual hallucinations + polysomnographic confirmation of REM sleep without atonia
E. Visual hallucinations + low uptake on MIBG scintigaphy
A. Cognitive fluctuations + severe neuroleptic sensitivity
What medications leads to falls in the elderly?
Highest risk to lowest risk:
- Antidepressants
- Neuroleptics, antipsychotics
- Benzos
- Sedatives
- Anti hypertensives
- NSAID
- Diuretics
- B blockers
- Narcotics
What medications leads to falls in the elderly?
Highest risk to lowest risk:
- Antidepressants
- Neuroleptics, antipsychotics
- Benzos
- Sedatives
- Anti hypertensives
- NSAID
- Diuretics
- B blockers
- Narcotics
Subcortical vs cortical dementia
Subcortical dementia include diseases which predominantly affects the basal ganglia along with features of cognitive decline
Examples include progressive supranuclear palsy, Huntington’s chorea, corticobasal degeneration, multiple system atrophy
Clinically: slowness of mental processing, forgetfulness, impaired cognition, lack of initiative/apathy, depressive symptoms (anhedonia, negative thoughts, loss of self esteem), extrapyramidal features (tremors and abnormal movements)
Cortical dementia, eg: Alzheimer’s Dementia
Clinically: aphasia, agnosia, and apraxia
